K-Vector

I asked whether tissue-specific AAV regulatory elements could be identified systematically from public single-cell chromatin data, and whether their mouse-to-human translatability could be predicted before any wet-lab work. To test this, I developed OrthoGate as the research method. It applies the same specificity, size, motif, and cross-species analysis across different cell types and returns a ranked list of candidate regulatory elements. Across seven cell types, the method recovered the expected identity gene as a top result in five, including INS in beta cells, GCG in alpha cells, RYR2 in heart cells, and OLFM4 in intestinal cells. It also rejected broadly active housekeeping genes and recovered known regulatory motifs. Most importantly, the analysis flagged candidates whose associated biology may not translate to mice, including PHGR1, an intestinal gene with no mouse ortholog. These results suggest that tissue-specific AAV regulatory elements can be identified computationally for multiple cell types, and that cross-species screening can meaningfully change which candidates should advance. This matters because it could reduce avoidable lab and animal studies and help prioritize safer, more translatable AAV designs for tissues outside the liver.